Abstract
Recruitment of CD2 to the immunological synapse in response to antigen is dependent on its proline-rich cytoplasmic tail. A peptide from this region (CD2:322-339) isolated CMS (human CD2AP); a related protein, CIN85; and the actin capping protein, CAPZ from a T cell line. In BIAcore analyses, the N-terminal SH3 domains of CMS and CIN85 bound CD2:322-339 with similar dissociation constants (KD = approximately 100 microm). CAPZ bound the C-terminal half of CMS and CIN85. Direct binding between CMS/CIN85 and CAPZ provides a link with the actin cytoskeleton. Overexpression of a fragment from the C-terminal half or the N-terminal SH3 domain of CD2AP in a mouse T cell hybridoma resulted in enhanced interleukin-2 production and reduced T cell receptor down-modulation in response to antigen. These adaptor proteins are important in T cell signaling consistent with a role for CD2 in regulating pathways initiated by CMS/CIN85 and CAPZ.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Antigens, CD / chemistry
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Binding Sites
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CD2 Antigens / chemistry*
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CD2 Antigens / metabolism
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CapZ Actin Capping Protein
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Carrier Proteins / chemistry*
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Carrier Proteins / metabolism
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Cytoskeletal Proteins*
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Humans
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Jurkat Cells
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Kinetics
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Microfilament Proteins / chemistry*
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Microfilament Proteins / metabolism
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Molecular Sequence Data
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Muscle Proteins / chemistry*
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Muscle Proteins / metabolism
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Peptide Fragments / chemistry
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Signal Transduction / immunology
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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T-Lymphocytes / immunology*
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src Homology Domains
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, CD
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CAPZA1 protein, human
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CD2 Antigens
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CD2-associated protein
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CapZ Actin Capping Protein
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Carrier Proteins
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Cytoskeletal Proteins
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Microfilament Proteins
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Muscle Proteins
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Peptide Fragments
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SH3KBP1 protein, human